Chroman derivatives

Abstract

Anti-hypertensive derivatives of trans-3-hydroxy-4-amino-chroman, their preparation from amines and chroman epoxide derivatives, and pharmaceutical compositions containing such anti-hypertensive derivatives for reducing blood pressure in mammals, including humans.

What we claim is: 
     
       1. A compound of the formula ##STR11## or a pharmaceutically acceptable acid addition salt thereof wherein R 1  is hydrogen or a hydrocarbon of 1 to 9 carbon atoms unsubstituted or substituted by hydroxyl or alkoxyl of 1 to 6 carbon atoms; R 2  is hydrogen or alkyl of 1 to 6 carbon atoms;   R 3  together with R 4  form a --CH═CH--CH═CH-- or --CH 2  --CH 2  --CH 2  --CH 2  -- ring system;   R 5  is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl; and   R 6  is hydrogen, alkyl of 1 to 6 carbon atoms or phenyl.   
     
     
       2. A compound according to claim 1 wherein R 1  is alkyl of 1 to 6 carbon atoms and R 2  is hydrogen or alkyl of 1 to 3 carbon atoms. 
     
     
       3. A compound according to claim 1 wherein the compound is of the formula (IV): ##STR12## or a pharmaceutically acceptable acid addition salt thereof wherein R 18  is of 1 to 6 carbon atoms, phenyl or benzyl; and R 3  together with R 4  form a --CH═CH--CH═CH--  or --CH 2  --CH 2  --CH 2  --CH 2  -- ring system. 
     
     
       4. A compound according to claim 3 wherein R 18  is isopropyl, isobutyl or t-butyl. 
     
     
       5. The compound according to claim 1 which is trans-4-isopropylamino-3,4-dihydro-2,2-dimethyl-2H-naphtho-[1,2-b]pyran-3-ol or a pharmaceutically acceptable addition salt thereof. 
     
     
       6. The compound according to claim 1 which is trans-4-tertiarylbutylamine-3,4-dihydro-2,2-dimethyl-2H-naphtho-[1,2-b]pyran-3-ol or a pharmaceutically acceptable acid addition salt thereof. 
     
     
       7. A compound according to claim 1 wherein R 5  and R 6  are each methyl. 
     
     
       8. A compound according to claim 1 of the formula (III): ##STR13## or a pharmaceutically acceptable acid addition salt thereof wherein NR 1  R 2  is a moiety NR 11  R 12  wherein R 11  is alkyl of 1 to 4 carbon atoms and R 12  is hydrogen, methyl or ethyl; R 9  is methyl or ethyl; and   R 10  is methyl or ethyl.   
     
     
       9. A compound according to claim 1 in the form of an acid addition salt wherein said salt is selected from the group consisting of the hydrochloride, hydrobromide, sulphate, phosphate, methane sulfonate, p-toluene sulfonate, acetate, propionate, succinate, citrate, tartrate, mandelate, lactate or gluconate. 
     
     
       10. A compound according to claim 1 wherein R 1  is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, hexyl, allyl, phenyl, benzyl, tolyl, cyclopropylmethyl, or cyclohexyl.   
     
     
       11. A compound according to claim 1 wherein R 1  is alkyl of 1 to 6 carbon atoms.   
     
     
       12. A compound according to claim 1 wherein R 2  is hydrogen, methyl, ethyl or propyl.   
     
     
       13. A compound according to claim 1 wherein R 5  and R 6  are each methyl or ethyl.   
     
     
       14. A compound according to claim 8 wherein the moiety NR 11  R 12  is a N(CH 3 ) 2  or NH-alkyl of 1 to 4 carbon atoms in the alkyl moiety. 
     
     
       15. A compound according to claim 1 wherein the moiety NR 1  R 2  is NHC(CH 3 ) 3  or NH--CH(CH 3 ) 2 . 
     
     
       16. The compound according to claim 1 which is trans-4-isopropylamino-3,4-dihydro-2,2-dimethyl-2H-naphtho[1,2-b]pyran-3-ol D-(+)-hydrogen tartrate. 
     
     
       17. The compound according to claim 1 which is trans-4-isopropylamino-3,4-dihydro-2H-naphtho[1,2b]-pyran-3-ol D-(+)-hydrogen tartrate hydrate. 
     
     
       18. A compound according to claim 8 wherein R 9  and R 10  are each methyl.